scholarly journals Oral and Nasal DNA Vaccines Delivered by Attenuated Salmonella enterica Serovar Typhimurium Induce a Protective Immune Response against Infectious Bronchitis in Chickens

2011 ◽  
Vol 18 (7) ◽  
pp. 1041-1045 ◽  
Author(s):  
Hongmei Jiao ◽  
Zhiming Pan ◽  
Yuelan Yin ◽  
Shizhong Geng ◽  
Lin Sun ◽  
...  
Keyword(s):  
Immune Responses ◽  
Salmonella Enterica ◽  
Dna Vaccines ◽  
Protective Efficacy ◽  
Nasal Administration ◽  
N Gene ◽  
Content Type ◽  
Infectious Bronchitis ◽  
Mucosal Vaccination ◽  
Serovar Typhimurium

ABSTRACTSeveral studies have reported that intramuscular injection of DNA vaccines against infectious bronchitis virus (IBV) induces protective immune responses. In the present study, we developed oral and nasal DNA vaccines that carried the S1 gene and N gene of IBV delivered by attenuatedSalmonella entericaserovar Typhimurium strains SL/pV-S1 and SL/pV-N, respectively. The safety and stability of recombinantSalmonellavaccine were evaluated. Following oral and nasal administration to chickens, the serum and mucosal samples were collected and antibodies against IBV were measured. Chickens were then challenged with IBV strain M41 by the nasal-ocular route 3 weeks after boosting. The results showed that oral and nasal immunization with coadministered SL/pV-S1 and SL/pV-N elicited significant IBV-specific humoral and mucosal immune responses and conferred protective efficacy against IBV challenge higher than that in chickens immunized only with SL/pV-S1. The current study shows that novel DNA vaccines delivered by attenuatedS.Typhimurium may be promising candidates for the prevention of infectious bronchitis (IB).These vaccines are efficacious, easily produced economically, and able to be delivered orally and nasally rather than injected. Coadministration of SL/pV-S1 and SL/pV-N may represent an effective mucosal vaccination regimen.

scholarly journals Flagellin from Recombinant Attenuated Salmonella enterica Serovar Typhimurium Reveals a Fundamental Role in Chicken Innate Immunity

2012 ◽  
Vol 19 (3) ◽  
pp. 304-312 ◽  
Author(s):  
Zhiming Pan ◽  
Qiuxia Cong ◽  
Shizhong Geng ◽  
Qiang Fang ◽  
Xilong Kang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Salmonella Enterica ◽  
Rational Design ◽  
Bacterial Load ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTRecombinant attenuatedSalmonellavaccines have been extensively studied, with a focus on eliciting specific immune responses against foreign antigens. However, very little is known about the innate immune responses, particularly the role of flagellin, in the induction of innate immunity triggered by recombinant attenuatedSalmonellain chickens. In the present report, we describe twoSalmonella entericaserovar Typhimurium vaccine strains, wild-type (WT) or flagellin-deficient (flhD)Salmonella, both expressing the fusion protein (F) gene of Newcastle disease virus. We examined the bacterial load and spatiotemporal kinetics of expression of inflammatory cytokine, chemokine, and Toll-like receptor 5 (TLR5) genes in the cecum, spleen, liver, and heterophils following oral immunization of chickens with the twoSalmonellastrains. TheflhDmutant exhibited an enhanced ability to establish systemic infection compared to the WT. In contrast, the WT strain induced higher levels of interleukin-1β (IL-1β), CXCLi2, and TLR5 mRNAs in cecum, the spleen, and the heterophils than theflhDmutant at different times postinfection. Collectively, the present data reveal a fundamental role of flagellin in the innate immune responses induced by recombinant attenuatedSalmonellavaccines in chickens that should be considered for the rational design of novel vaccines for poultry.

scholarly journals Toll-Like Receptor 5-Dependent Immunogenicity and Protective Efficacy of a Recombinant Fusion Protein Vaccine Containing the Nontoxic Domains of Clostridium difficile Toxins A and B and Salmonella enterica Serovar Typhimurium Flagellin in a Mouse Model of Clostridium difficile Disease

2013 ◽  
Vol 81 (6) ◽  
pp. 2190-2196 ◽  
Author(s):  
Chandrabali Ghose ◽  
Janneke M. Verhagen ◽  
Xinhua Chen ◽  
Jian Yu ◽  
Yaoxing Huang ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Mouse Model ◽  
Salmonella Enterica ◽  
Animal Studies ◽  
Protective Efficacy ◽  
Protein Vaccine ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Toll Like Receptor 5 ◽  
High Level

ABSTRACTClostridium difficileis a spore-forming bacillus that produces toxin-mediated enteric disease.C. difficileexpresses two major virulence factors, toxin A (TcdA) and toxin B (TcdB). Human and animal studies demonstrate a clear association between humoral immunity to these toxins and protection againstC. difficileinfection (CDI). The receptor binding-domains (RBDs) of TcdA and TcdB are known to be immunogenic. Here, we tested the immunoadjuvant properties ofSalmonella entericaserovar Typhimurium flagellin (FliC) subunit D1 as an innate immune agonist expressed as a recombinant fusion vaccine targeting the RBDs of TcdA and TcdB in mice. Intraperitoneally immunized mice developed prominent anti-TcdA and anti-TcdB immunoglobulin G in serum. The protective efficacy of the recombinant vaccines, with or without an adjuvant, was tested in a mouse model of CDI that closely represents the human disease. Following intraperitoneal immunization equivalent to two doses of toxoid A and toxoid B vaccine adjuvanted with alum and oral challenge withC. difficileVPI 10463, C57BL/6 mice were able to mount a protective immune response that prevented diarrhea and death compared to mice immunzed with alum alone. These results are significantly different from those for control mice (P< 0.001). These results provide evidence that a recombinant protein-based vaccine targeting the RBDs of theC. difficiletoxins adjuvanted withS. Typhimurium flagellin can induce rapid, high-level protection in a mouse model of CDI when challenged with the homologous strain from which the vaccine antigens were derived and warrant further preclinical testing against clinically relevantC. difficilestrains in the mouse and hamster models of CDI.

scholarly journals Construction and Immunological Evaluation of Dual Cell Surface Display of HIV-1 Gag and Salmonella enterica Serovar Typhimurium FliC in Lactobacillus acidophilus for Vaccine Delivery

2012 ◽  
Vol 19 (9) ◽  
pp. 1374-1381 ◽  
Author(s):  
Akinobu Kajikawa ◽  
Lin Zhang ◽  
Julie Long ◽  
Shila Nordone ◽  
Laura Stoeker ◽  
...  
Keyword(s):  
Cell Surface ◽  
Immune Responses ◽  
Signal Peptide ◽  
Lactobacillus Acidophilus ◽  
Bacterial Cell ◽  
Salmonella Enterica ◽  
Oral Vaccines ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Hiv 1

ABSTRACTOral vaccines that elicit a mucosal immune response may be effective against human immunodeficiency virus type 1 (HIV-1) because its transmission occurs mainly at the mucosa. The aim of this study was to construct recombinantLactobacillusfor oral delivery of oral vaccines against HIV-1 and to evaluate their immunogenicity. A recombinantLactobacillus acidophilusstrain expressing the HIV-1 Gag on the bacterial cell surface was established by fusion with the signal peptide and anchor motif of a mucus binding protein (Mub) fromL. acidophiluswith or without coexpression ofSalmonella entericaserovar Typhimurium flagellin (FliC) fused to a different Mub signal peptide and anchor. Using HEK293 cells engineered to express Toll-like receptor 5 (TLR5), the biological activity of FliC on the bacterial cell surfaces was determined. The surface-exposed flagellin retained its TLR5-stimulating activity, suggesting that the recombinant strain with Gag and FliC dual display might provide a different immunopotency than the strain expressing only Gag. The immunological properties of the recombinant strains were assessed by coculture with human myeloid dendritic cells (DCs). The heterologous antigens on the cell surface affected maturation and cytokine responses of DCs. Acquired immune responses were also investigated by intragastric immunization of mice. The enzyme-linked immunosorbent spot assay showed induction of gamma interferon-producing cells at local mucosa after immunization of mice with the Gag-producing strain. Meanwhile, the immunization withL. acidophilusdisplaying both Gag and FliC resulted in an increase of Gag-specific IgA-secreting cells. These results suggested that the Gag-displayingL. acidophiluselicited specific immune responses and the coexistence of FliC conferred an adjuvant effect on local IgA production.

scholarly journals Efficiency of Conditionally Attenuated Salmonella enterica Serovar Typhimurium in Bacterium-Mediated Tumor Therapy

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Michael Frahm ◽  
Sebastian Felgner ◽  
Dino Kocijancic ◽  
Manfred Rohde ◽  
Michael Hensel ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Tumor Targeting ◽  
Antitumor Effect ◽  
Treatment Options ◽  
Tumor Therapy ◽  
Therapeutic Benefit ◽  
Industrialized Countries ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Therapeutic Molecules

ABSTRACTIncreasing numbers of cancer cases generate a great urge for new treatment options. Applying bacteria likeSalmonella entericaserovar Typhimurium for cancer therapy represents an intensively explored option. These bacteria have been shown not only to colonize solid tumors but also to exhibit an intrinsic antitumor effect. In addition, they could serve as tumor-targeting vectors for therapeutic molecules. However, the pathogenicS. Typhimurium strains used for tumor therapy need to be attenuated for safe application. Here, lipopolysaccharide (LPS) deletion mutants (ΔrfaL, ΔrfaG, ΔrfaH, ΔrfaD, ΔrfaP, and ΔmsbBmutants) ofSalmonellawere investigated for efficiency in tumor therapy. Of such variants, the ΔrfaDand ΔrfaGdeep rough mutants exhibited the best tumor specificity and lowest pathogenicity. However, the intrinsic antitumor effect was found to be weak. To overcome this limitation, conditional attenuation was tested by complementing the mutants with an inducible arabinose promoter. The chromosomal integration of the respective LPS biosynthesis genes into thearaBADlocus exhibited the best balance of attenuation and therapeutic benefit. Thus, the present study establishes a basis for the development of an applicably cancer therapeutic bacterium.IMPORTANCECancer has become the second most frequent cause of death in industrialized countries. This and the drawbacks of routine therapies generate an urgent need for novel treatment options. Applying appropriately modifiedS. Typhimurium for therapy represents the major challenge of bacterium-mediated tumor therapy. In the present study, we demonstrated thatSalmonellabacteria conditionally modified in their LPS phenotype exhibit a safe tumor-targeting phenotype. Moreover, they could represent a suitable vehicle to shuttle therapeutic compounds directly into cancerous tissue without harming the host.

scholarly journals Whole-Genome Sequence of Salmonella enterica subsp. enterica Serovar Typhimurium Strain UPM 260, Isolated from a Broiler Chicken in Perak, Malaysia

2017 ◽  
Vol 5 (46) ◽  
Author(s):  
Najwa Syahirah Roslan ◽  
Shagufta Jabeen ◽  
Nurulfiza Mat Isa ◽  
Abdul Rahman Omar ◽  
Mohd Hair Bejo ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Salmonella Enterica ◽  
Broiler Chicken ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Typhimurium Strain ◽  
Serovar Typhimurium

ABSTRACT Salmonella enterica subsp. enterica serovar Typhimurium is one of several well-categorized Salmonella serotypes recognized globally. Here, we report the whole-genome sequence of S. Typhimurium strain UPM 260, isolated from a broiler chicken.

scholarly journals Association of a Protective Monoclonal IgA with the O Antigen of Salmonella enterica Serovar Typhimurium Impacts Type 3 Secretion and Outer Membrane Integrity

2012 ◽  
Vol 80 (7) ◽  
pp. 2454-2463 ◽  
Author(s):  
Stephen J. Forbes ◽  
Daniel Martinelli ◽  
Chyongere Hsieh ◽  
Jeffrey G. Ault ◽  
Michael Marko ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Epithelial Cells ◽  
Outer Membrane ◽  
Salmonella Enterica ◽  
Membrane Integrity ◽  
Effector Proteins ◽  
Content Type ◽  
O Antigen ◽  
Serovar Typhimurium ◽  
Type 3

ABSTRACTInvasion of intestinal epithelial cells bySalmonella entericaserovar Typhimurium is an energetically demanding process, involving the transfer of effector proteins from invading bacteria into host cells via a specialized organelle known as theSalmonellapathogenicity island 1 (SPI-1) type 3 secretion system (T3SS). By a mechanism that remains poorly understood, entry ofS. Typhimurium into epithelial cells is inhibited by Sal4, a monoclonal, polymeric IgA antibody that binds an immunodominant epitope within the O-antigen (O-Ag) component of lipopolysaccharide. In this study, we investigated how the binding of Sal4 to the surface ofS. Typhimurium influences T3SS activity, bacterial energetics, and outer membrane integrity. We found that Sal4 treatment impaired T3SS-mediated translocon formation and attenuated the delivery of tagged effector proteins into epithelial cells. Sal4 treatment coincided with a partial reduction in membrane energetics and intracellular ATP levels, possibly explaining the impairment in T3SS activity. Sal4's effects on bacterial secretion and energetics occurred concurrently with an increase in O-Ag levels in culture supernatants, alterations in outer membrane permeability, and changes in surface ultrastructure, as revealed by transmission electron microscopy and cryo-electron microscopy. We propose that Sal4, by virtue of its ability to bind and cross-link the O-Ag, induces a form of outer membrane stress that compromises the integrity of theS. Typhimurium cell envelope and temporarily renders the bacterium avirulent.

scholarly journals Draft Genome Sequence of Lactobacillus fermentum Lf2, an Exopolysaccharide-Producing Strain Isolated from Argentine Cheese

2018 ◽  
Vol 7 (18) ◽  
Author(s):  
Hugh M. B. Harris ◽  
Elisa C. Ale ◽  
Jorge A. Reinheimer ◽  
Ana G. Binetti ◽  
Paul W. O’Toole
Keyword(s):  
Genome Sequence ◽  
Salmonella Enterica ◽  
Draft Genome ◽  
Protective Role ◽  
Lactobacillus Fermentum ◽  
Draft Genome Sequence ◽  
Content Type ◽  
Serovar Typhimurium ◽  
High Concentrations

Lactobacillus fermentum Lf2, an Argentine cheese isolate, can produce high concentrations of exopolysaccharides (EPS). These EPS were shown to improve the texture and rheology of yogurt, as well as to play a protective role in mice exposed to Salmonella enterica serovar Typhimurium.

scholarly journals Regulation of RamA by RamR in Salmonella enterica Serovar Typhimurium: Isolation of a RamR Superrepressor

2012 ◽  
Vol 56 (11) ◽  
pp. 6037-6040 ◽  
Author(s):  
Vito Ricci ◽  
Stephen J. W. Busby ◽  
Laura J. V. Piddock
Keyword(s):  
Transcription Factor ◽  
Salmonella Enterica ◽  
Fluorescent Protein ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Promoter Sequence ◽  
Palindromic Sequence ◽  
Content Type ◽  
Gfp Reporter ◽  
Serovar Typhimurium ◽  
Green Fluorescent

ABSTRACTRamA is a transcription factor involved in regulating multidrug resistance inSalmonella entericaserovar Typhimurium SL1344. Green fluorescent protein (GFP) reporter fusions were exploited to investigate the regulation of RamA expression by RamR. We show that RamR represses theramApromoter by binding to a palindromic sequence and describe a superrepressor RamR mutant that binds to theramApromoter sequence more efficiently, thus exhibiting aramAinactivated phenotype.

scholarly journals Curcumin Reduces the Motility of Salmonella enterica Serovar Typhimurium by Binding to the Flagella, Thereby Leading to Flagellar Fragility and Shedding

2016 ◽  
Vol 198 (13) ◽  
pp. 1798-1811 ◽  
Author(s):  
Sandhya Amol Marathe ◽  
Arjun Balakrishnan ◽  
Vidya Devi Negi ◽  
Deepika Sakorey ◽  
Nagasuma Chandra ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Binding Assay ◽  
Protein A ◽  
Intestinal Barrier ◽  
Site Directed Mutagenesis ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Flagellar Filament ◽  
Fluorescence Binding ◽  
Fluorescence Binding Assay

ABSTRACTOne of the important virulence properties of the pathogen is its ability to travel to a favorable environment, cross the viscous mucus barrier (intestinal barrier for enteric pathogens), and reach the epithelia to initiate pathogenesis with the help of an appendage, like flagella. Nonetheless, flagella can act as an “Achilles heel,” revealing the pathogen's presence to the host through the stimulation of innate and adaptive immune responses. We assessed whether curcumin, a dietary polyphenol, could alter the motility ofSalmonella, a foodborne pathogen. It reduced the motility ofSalmonella entericaserovar Typhimurium by shortening the length of the flagellar filament (from ∼8 μm to ∼5 μm) and decreasing its density (4 or 5 flagella/bacterium instead of 8 or 9 flagella/bacterium). Upon curcumin treatment, the percentage of flagellated bacteria declined from ∼84% to 59%. However, no change was detected in the expression of the flagellin gene and protein. A fluorescence binding assay demonstrated binding of curcumin to the flagellar filament. This might make the filament fragile, breaking it into smaller fragments. Computational analysis predicted the binding of curcumin, its analogues, and its degraded products to a flagellin molecule at an interface between domains D1 and D2. Site-directed mutagenesis and a fluorescence binding assay confirmed the binding of curcumin to flagellin at residues ASN120, ASP123, ASN163, SER164, ASN173, and GLN175.IMPORTANCEThis work, to our knowledge the first report of its kind, examines how curcumin targets flagellar density and affects the pathogenesis of bacteria. We found that curcumin does not affect any of the flagellar synthesis genes. Instead, it binds to the flagellum and makes it fragile. It increases the torsional stress on the flagellar filament that then breaks, leaving fewer flagella around the bacteria. Flagella, which are crucial ligands for Toll-like receptor 5, are some of the most important appendages ofSalmonella. Curcumin is an important component of turmeric, which is a major spice used in Asian cooking. The loss of flagella can, in turn, change the pathogenesis of bacteria, making them more robust and fit in the host.

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